Gene Therapy Clinical Study in Adult PKU (pheNIX)

• ClinicalTrials.gov Identifier: NCT03952156
• Recruitment Status: Active, not recruiting
• First Posted: May 16, 2019
• Last Update Posted: March 2, 2023
• Sponsor: Homology Medicines, Inc
• Information provided by (Responsible Party): Homology Medicines, Inc

Study Description

Brief Summary:

This is a Phase 1/2, open-label, randomized, concurrently-controlled, dose escalation study to evaluate the safety and efficacy of HMI-102 in adult PKU subjects with PAH deficiency. Participants will receive a single administration of HMI-102 and will be followed for safety and efficacy for 1 year.

Condition or disease	Intervention/treatment	Phase
Phenylketonurias; PAH Deficiency	Genetic: HMI-102	Phase 1; Phase 2

Detailed Description:

Part 1 of this study will evaluate the safety and efficacy of HMI-102 gene therapy in adult subjects with PKU due to PAH deficiency. Subjects will receive a single dose of HMI-102 administered intravenously. Up to 3 dose levels of HMI-102 may be investigated in this study. At a given dose level, a minimum of 2 subjects will be enrolled and dosed. Dosing of the first two subjects will be staggered. Following evaluation of data from the first 2 subjects in a cohort, a decision can be made to either escalate to the next dose level or expand the cohort at the selected dose level. Additional doses may be added by HMI to investigate intermediate or higher doses.

In Part 2 dose expansion, evaluation of up to 2 dose levels is planned. Subjects will be randomized to receive HMI-102 or a concurrent delayed treatment control arm. Subjects in the delayed treatment control will be eligible to receive HMI-102 after 28 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Open-Label, Randomized, Concurrently-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of HMI-102 in Adult PKU Subjects With PAH Deficiency
• Actual Study Start Date: June 10, 2019
• Actual Primary Completion Date: January 10, 2023
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Dose Level 1 of HMI-102 delivered intravenously one time	Genetic: HMI-102; HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Cohort 2; Dose Level 2 of HMI-102 delivered intravenously one time	Genetic: HMI-102; HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Cohort 3; Dose Level 3 of HMI-102 delivered intravenously one time	Genetic: HMI-102; HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Delayed Treatment Control; Delayed Treatment Control Arm	Genetic: HMI-102; Control subjects will generally have the same assessments as treated subjects. Control subjects will undergo pre-baseline procedures to confirm that they are eligible to receive treatment with HMI-102. Once eligible control subjects are dosed with HMI-102, they will initiate the same post-dose procedures as subjects who received HMI-102.
Experimental: Expansion Phase First Dose level; Expansion Phase First Dose Level of HMI-102 delivered intravenously one time	Genetic: HMI-102; HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Expansion Phase Second Dose level; Expansion Phase Second Dose Level of HMI-102 delivered intravenously one time	Genetic: HMI-102; HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]
   Subjects with at least one TEAE or serious TEAE
2. Change from baseline in clinical laboratory values (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]
   Change in serum chemistry values including liver function tests, hematology, and urinalysis
3. Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]
   Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations
4. Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 28 weeks post dose (Dose Escalation Phase) [ Time Frame: Week 28 ]
   Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 28 weeks post dose
5. Change from baseline in Plasma Phe Concentration (Dose Escalation Phase) [ Time Frame: Weeks 24-28 ]
   Change from baseline in plasma Phe concentration during Weeks 24-28
6. Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase) [ Time Frame: Weeks 24-28 ]
   Change from baseline in mean plasma Phe concentration during Weeks 24-28

Secondary Outcome Measures :

1. Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Baseline to Week 28 ]
   Subjects achieving plasma Phe concentration thresholds up to Week 28 post administration of HMI-102
2. Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Baseline to Week 52 ]
   Subjects achieving plasma Phe concentration thresholds up to Week 52 post administration of HMI-102
3. Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Week 52 ]
   Subject Achieving a change from baseline in total protein intake at Week 52 post-administration of HMI-102
4. Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase) [ Time Frame: Baseline to Week 52 ]
   Subjects with at least one TEAE or serious TEAE

Other Outcome Measures:

1. Phenylketonuria Quality of Life Questionnaire (PKU-QOL) [ Time Frame: Baseline to Week 52 ]
   Change in PKU-QOL

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Adults 18-55 years of age at the time of informed consent
• Diagnosis of phenylketonuria (PKU) due to PAH deficiency
• Two plasma Phe values with a concentration of ≥ 600 μmol/L drawn at least 72 hours apart during the screening period and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
• Subject has the ability and willingness to maintain their baseline diet, whether Phe-restricted or unrestricted for the duration of the trial, unless otherwise directed

Key Exclusion Criteria:

• Subjects with PKU that is not due to PAH deficiency
• Presence of anti-AAVHSC15 neutralizing antibodies
• ALT > ULN and AST > ULN
• Alkaline phosphatase > ULN.
• Total bilirubin > ULN, direct bilirubin > ULN
• Serum creatinine >1.5x ULN
• International normalized ratio (INR) > 1.2
• Hematology values outside of the normal range (hemoglobin <11.0 g/dL for males or <10.0 g/dL for females; white blood cells (WBC) <3,000/μL; absolute neutrophils <1500/μL; platelets <100,000/μL)
• Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
• Any clinically significant abnormal laboratory result at screening, in the opinion of the Investigator
• Contraindication to corticosteroid use or conditions that could worsen in the presence of corticosteroids, as assessed and determined by the investigator
• Previously received gene therapy for the treatment of any condition.

Contacts and Locations

Locations

United States, California

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States, 90027

Children's Hospital of Orange County

Orange, California, United States, 92868

United States, Florida

University of South Florida

Tampa, Florida, United States, 33606

United States, Georgia

Emory University Hospital

Atlanta, Georgia, United States, 30322

United States, Illinois

Lurie Children's Hospital of Chicago

Chicago, Illinois, United States, 60611

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

United States, North Carolina

The University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15224

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75235

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84108

Sponsors and Collaborators

Homology Medicines, Inc

Investigators

• Principal Investigator: Olaf A Bodamer, M.D.; Boston Children's Hospital

More Information

• Responsible Party: Homology Medicines, Inc
• ClinicalTrials.gov Identifier: NCT03952156
• Other Study ID Numbers: HMI-102-101
• First Posted: May 16, 2019
• Last Update Posted: March 2, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Homology Medicines, Inc:

PKU; Phenylketonuria; PAH Deficiency; Hyperphenylalaninemia; Phenylalanine; Adeno Associated Virus; AAVHSC15

Additional relevant MeSH terms:

Phenylketonurias; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases